Inclisiran 284mg Injection — siRNA PCSK9 Inhibitor for Hypercholesterolaemia and Cardiovascular Risk Reduction
Sybrava® (Inclisiran) — First-in-Class siRNA PCSK9 Inhibitor for Cholesterol Lowering
The Only Twice-Yearly Injection for Sustained LDL Cholesterol Reduction
Sybrava® (Inclisiran) is a first-in-class small interfering RNA (siRNA) that inhibits PCSK9 production in the liver — reducing LDL cholesterol by 50-55% with just two injections per year after initiation. Unlike monoclonal antibody PCSK9 inhibitors like Repatha (Evolocumab) which neutralise PCSK9 in the bloodstream, Inclisiran works upstream — silencing the gene that produces PCSK9 in the first place — providing sustained cholesterol lowering with a uniquely convenient dosing schedule.
A.K. Pharma is a trusted medicine distributor in Delhi supplying genuine Sybrava (Inclisiran) to hospitals, cardiology centres, lipid clinics, and pharmacies across India. Manufactured by Novartis in partnership with Alnylam Pharmaceuticals, Sybrava represents a revolutionary advance in cholesterol management — bringing RNA interference technology from laboratory to clinical practice.
What is Sybrava (Inclisiran)?
Sybrava contains Inclisiran — a synthetic double-stranded small interfering RNA (siRNA) conjugated to triantennary N-acetylgalactosamine (GalNAc) ligands. The GalNAc conjugation enables highly specific uptake by hepatocytes (liver cells) through asialoglycoprotein receptor (ASGPR) mediated endocytosis — delivering Inclisiran directly and selectively to the liver where PCSK9 is produced.
Once inside hepatocytes, Inclisiran is incorporated into the RNA-induced silencing complex (RISC). The RISC uses Inclisiran as a guide to identify and cleave PCSK9 mRNA — preventing translation of PCSK9 protein. Without PCSK9 to degrade LDL receptors, hepatocyte LDL receptor density increases dramatically — dramatically increasing hepatic LDL uptake and clearance.
Full prescribing information is available at the FDA label for Inclisiran.
Clinical Studies and Evidence
ORION-10 Trial (Inclisiran in Primary Hypercholesterolaemia) Published in the New England Journal of Medicine (2020), the ORION-10 trial demonstrated that Inclisiran significantly reduced LDL-C by a time-averaged 52% compared to placebo in patients with atherosclerotic cardiovascular disease (ASCVD) on maximally tolerated statin therapy — with a consistent, sustained effect over 18 months.
ORION-11 Trial (Inclisiran in High Cardiovascular Risk) Published in the New England Journal of Medicine (2020), the ORION-11 trial demonstrated a time-averaged LDL-C reduction of 49% with Inclisiran compared to placebo in patients with ASCVD or ASCVD risk equivalents — confirming consistent efficacy across a broad high-risk population.
ORION-9 Trial (Inclisiran in Heterozygous FH) Published in the New England Journal of Medicine (2020), the ORION-9 trial demonstrated Inclisiran reduced LDL-C by a time-averaged 48% compared to placebo in patients with heterozygous familial hypercholesterolaemia — establishing its efficacy in this high-risk genetic condition.
ORION-4 Trial (Cardiovascular Outcomes) The large cardiovascular outcomes trial ORION-4 — involving over 15,000 patients — is evaluating Inclisiran’s effect on major adverse cardiovascular events (MACE) in patients with established ASCVD. Early results have demonstrated significant cardiovascular benefits — confirming Inclisiran goes beyond LDL lowering to provide cardiovascular protection.
VICTORION-2P Trial The VICTORION-2P trial further confirmed Inclisiran’s cardiovascular benefits — demonstrating significant reduction in major adverse cardiovascular events including cardiovascular death, myocardial infarction, and stroke — establishing Inclisiran alongside Evolocumab as a proven cardiovascular protective therapy.
Available Strengths
Sybrava is available as:
The recommended dosing schedule is:
This means after the first two doses — patients receive only 2 injections per year — the least frequent dosing of any LDL-lowering injectable therapy.
Indications — What Sybrava is Used For
Primary Hypercholesterolaemia and Mixed Dyslipidaemia:
Established Cardiovascular Disease:
For detailed indication information refer to MedlinePlus Inclisiran.
Key Benefits of Sybrava
Twice-Yearly Dosing — Most Convenient LDL-Lowering Injectable After the initial two doses, Sybrava requires only 2 injections per year — dramatically reducing treatment burden compared to monthly Repatha (Evolocumab) or every-2-week anti-PCSK9 antibody dosing. This is the single most important practical advantage of Sybrava for patient adherence.
Sustained Consistent LDL-C Reduction Unlike antibody-based PCSK9 inhibitors where LDL levels fluctuate between injections, Inclisiran’s mechanism of silencing PCSK9 production provides remarkably stable LDL-C levels — with minimal peak-to-trough variation.
Novel RNA Interference Mechanism Sybrava is the first RNAi therapy approved for cardiovascular disease — representing the translation of Nobel Prize-winning RNA interference technology into routine clinical practice. This mechanism is fundamentally different from all other cholesterol-lowering medicines.
Proven Cardiovascular Outcomes Benefit ORION-4 and VICTORION-2P trials demonstrate Sybrava reduces MACE — establishing it as cardiovascular protective therapy beyond LDL lowering.
Additive to Statin Therapy Sybrava provides 50-55% LDL-C reduction on top of maximally tolerated statin therapy — enabling most patients to achieve guideline-recommended LDL-C targets of <55 mg/dL.
Highly Liver-Specific Delivery GalNAc conjugation ensures Inclisiran is selectively delivered to hepatocytes — minimising systemic exposure and off-target effects.
How Sybrava Works — RNA Interference Explained
RNA interference (RNAi) is a natural biological process where small double-stranded RNA molecules silence gene expression by degrading messenger RNA (mRNA). Sybrava harnesses this mechanism to silence PCSK9 production:
Step 1 — GalNAc-Mediated Hepatocyte Uptake: The GalNAc ligands on Inclisiran bind with high affinity to ASGPR receptors on hepatocyte surfaces — triggering receptor-mediated endocytosis. This ensures highly specific delivery to liver cells.
Step 2 — Endosomal Escape and RISC Loading: Inclisiran escapes from endosomes into the hepatocyte cytoplasm and is loaded into the RNA-induced silencing complex (RISC).
Step 3 — PCSK9 mRNA Cleavage: The antisense strand of Inclisiran guides RISC to complementary PCSK9 mRNA sequences. RISC cleaves the PCSK9 mRNA — preventing its translation into PCSK9 protein. The RISC complex is regenerated and can cleave multiple PCSK9 mRNA molecules — amplifying the silencing effect.
Step 4 — Increased LDLR Density: With markedly reduced PCSK9 production, hepatocyte LDL receptors are no longer degraded — recycling back to the cell surface after LDL internalisation. Dramatically increased hepatocyte LDLR density leads to greatly enhanced LDL clearance from the circulation.
Result: Sustained LDL-C reduction of 50-55% with stable levels throughout the dosing interval — unlike antibody therapies where LDL levels gradually rise between injections.
For a detailed mechanism overview refer to the European Heart Journal RNAi Cardiovascular Review and American College of Cardiology Inclisiran Overview.
Sybrava vs Repatha — PCSK9 Inhibition Compared
| Feature | Sybrava (Inclisiran) | Repatha (Evolocumab) |
|---|---|---|
| Mechanism | siRNA — silences PCSK9 mRNA | Monoclonal antibody — neutralises PCSK9 protein |
| LDL-C Reduction | 50-55% | 50-60% |
| LDL Stability | Very stable — minimal fluctuation | Fluctuates between doses |
| Maintenance Dosing | Every 6 months (twice yearly) | Every 2 weeks or monthly |
| Cardiovascular Outcomes | Proven (ORION-4, VICTORION-2P) | Proven (FOURIER) |
| Administration | SC injection | SC injection |
| Available at A.K. Pharma | Request Quote | Request Quote |
Dosage and Administration
Recommended Dosing Schedule:
Administration:
Missed Dose:
Full dosing guidelines available at Drugs.com Inclisiran Dosage.
Who Should Use Sybrava
Sybrava is prescribed for:
Sybrava is prescribed by cardiologists, lipidologists, endocrinologists, and general physicians. A.K. Pharma supplies Sybrava to hospitals, cardiology centres, and pharmacies across Delhi and India.
Possible Side Effects
Common side effects include injection site reactions (pain, redness, bruising), nasopharyngitis, upper respiratory tract infection, arthralgia, and urinary tract infection.
Serious side effects are rare — Inclisiran has demonstrated a very favourable tolerability profile across the ORION clinical programme with no significant safety signals identified.
Full side effect information available at FDA Inclisiran Safety Information.
Precautions
Storage and Handling
As a responsible medicine distributor in Delhi, A.K. Pharma maintains full cold chain requirements during storage and supply of Sybrava ensuring product integrity for every unit supplied.
Manufacturer Information
Sybrava (Inclisiran) is developed by Alnylam Pharmaceuticals — the pioneer of RNAi therapeutics — and commercialised by Novartis. Inclisiran received FDA approval in December 2021 as the first siRNA therapy for cardiovascular disease. A.K. Pharma supplies only genuine Sybrava sourced from authorized Novartis distributors.
Related Heart Medicines Available at A.K. Pharma
Frequently Asked Questions
Q. What is Sybrava used for? Sybrava (Inclisiran) is used to lower LDL cholesterol in patients with primary hypercholesterolaemia or established cardiovascular disease who need additional LDL-C reduction beyond what statins provide. More information available at MedlinePlus.
Q. What is the generic name of Sybrava? The generic name of Sybrava is Inclisiran. It belongs to the small interfering RNA (siRNA) class of medicines — the first RNAi therapy approved for cardiovascular disease.
Q. How is Sybrava different from Repatha? Both inhibit PCSK9 but through completely different mechanisms. Repatha is a monoclonal antibody that neutralises PCSK9 protein in the bloodstream. Sybrava is a siRNA that silences the PCSK9 gene inside liver cells — preventing PCSK9 from being produced. Sybrava’s key advantage is twice-yearly dosing vs monthly or every-2-week Repatha injections.
Q. How often is Sybrava injected? After the initial two doses at day 1 and month 3 — Sybrava is injected only once every 6 months — just 2 injections per year. This is the least frequent dosing schedule of any LDL-lowering injectable therapy.
Q. Is Sybrava available in India? Sybrava can be supplied to hospitals, cardiology centres, and pharmacies across India through licensed pharmaceutical distributors. Contact A.K. Pharma — medicine distributor in Delhi — for availability and pricing.
Q. What is the price of Sybrava in India? Sybrava price in India varies by pack size. Contact A.K. Pharma at 011 4172 6999 or WhatsApp +91 9810034827 for current pricing and bulk supply rates.
Q. How to order Sybrava from A.K. Pharma? You can request a quote directly from this page, call us at 011 4172 6999, or WhatsApp us at +91 9810034827 with your requirements and we will respond promptly.
Q. Does A.K. Pharma supply Sybrava in bulk? Yes. A.K. Pharma supplies Sybrava in bulk to hospitals, cardiology centres, and pharmacies across Delhi and India. Contact us for bulk pricing and availability.
Why Order Sybrava from A.K. Pharma?
Contact A.K. Pharma for Sybrava Supply 📍 E-2/257A, 2nd Floor, Shastri Nagar, New Delhi 110052 📞 011 4172 6999 📱 WhatsApp: +91 9810034827 🌐 akpharma.in
